Cannabinoids are compounds derived from Cannabis sativa, an annual plant in the Cannabaceae family. The plant contains about 60 cannabinoids. The most active naturally occurring cannabinoid is tetrahydrocannabinol (THC), which is used for the treatment of a wide range of medical conditions, including glaucoma, AIDS wasting, neuropathic pain, treatment of spasticity associated with multiple sclerosis, fibromyalgia and chemotherapy-induced nausea. Additionally, THC has been reported to exhibit a therapeutic effect in the treatment of allergies, inflammation, infection, epilepsy, depression, migraine, bipolar disorders, anxiety disorder, and drug dependency and withdrawal syndromes. THC is particularly effective as an anti-emetic drug and is administered to curb emesis, a common side effect accompanying the use of opioid analgesics and anesthetics, highly active anti-retroviral therapy and cancer chemotherapy.
Cannabinoids are lipophilic and potentially acid-labile compounds. Because of their hydrophobic nature, cannabinoids are poorly absorbed systemically from oral dosage forms because of the poor dissolution of cannabinoids in the aqueous environment of gastrointestinal tract. Oral formulations of cannabinoids, therefore, exhibit low bioavailability.
Δ9-tetrahydrocannabinol is prone to oxidation, Prolonged contact with air results in the gradual oxidation of Δ9-tetrahydrocannabinol to cannabinol (CBN). There are currently two oral formulations of Δ9-tetrahydrocannabinol commercially available by prescription in the United States: Dronabinol, is available commercially as Marinol® soft gelatin capsules and Namisol® is available as sublingual tablets, have been approved by the Food and Drug Administration (FDA) for the control of nausea and vomiting associated with chemotherapy and for appetite stimulation in AIDS patients suffering from the wasting syndrome. Marinol® is formulated by dissolving Δ9-tetrahydrocannabinol in sesame oil to manufacture soft gelatin capsules suitable for oral administration. Marinol® is expensive and gelatin capsules of Marinol® exhibit full therapeutic potency approximately one hour following their administration.
Onset of therapeutic potency for Dronabinol is shorter, approximately 0.5 to 1 hour after oral administration, with a peak therapeutic effect lasting for a time period of 2-4 hours post administration. However, the amount of Dronabinol reaching the blood stream by absorption through the digestive system is only 10-20% of the administered dose. Fasting or food deprivation may further decrease the rate of absorption of Dronabinol.
On the other hand, Namisol® has a rapid uptake through the sublingual mucosa. However, the tablet, has to be kept under the tongue for the time it takes to dissolve and stimulates the flow of saliva. This make it difficult for patients to avoid swallowing the tablet when substantial amounts of saliva are produced.
Oral formulations of synthetic cannabionoids are also available commercially. For instance, Nabilone is a synthetic cannabinoid marketed as Cesamet® in Canada the United States, the United Kingdom and Mexico. Nabilone is formulated as capsules suitable for oral administration. Cesamet® is approved for use as an antiemetic and analgesic for neuropathic pain. Sativex®, is a mouth spray containing tetrahydrocannabinol (THC) and cannabidiol (CBD). It is approved for the treatment of spasticity due to multiple sclerosis. Administration of synthetic cannabinoid formulations show fewer undesirable side effects than THC.
Because of their poor absorption and poor bioavailability, oral formulations have the additional disadvantage that they require several administrations a day, making it inconvenient for patients who have difficulty swallowing.
Accordingly, there is an urgent need in the art for oral formulations of cannabinoids with improved dissolution and taste and enhanced bioavailability and absorption, while at the same time do not cause gastrointestinal irritation. The present invention satisfies this need.